RNA splicing alterations are widespread and play critical roles in cancer pathogenesis and therapy.Lung cancer is highly heterogeneous and causes the most cancer-related deaths worldwide.Large-scale multi-omics studie...RNA splicing alterations are widespread and play critical roles in cancer pathogenesis and therapy.Lung cancer is highly heterogeneous and causes the most cancer-related deaths worldwide.Large-scale multi-omics studies have not only characterized the mutational landscapes but also discovered a plethora of transcriptional and post-transcriptional changes in lung cancer.Such resources have greatly facilitated the development of new diagnostic markers and therapeutic options over the past two decades.Intriguingly,altered RNA splicing has emerged as an important molecular feature and therapeutic target of lung cancer.In this review,we provide a brief overview of splicing dysregulation in lung cancer and summarize the recent progress on key splicing events and splicing factors that contribute to lung cancer pathogenesis.Moreover,we describe the general strategies targeting splicing alterations in lung cancer and highlight the potential of combining splicing modulation with currently approved therapies to combat this deadly disease.This review provides new mechanistic and therapeutic insights into splicing dysregulation in cancer.展开更多
RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomar...RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomarkers and therapeutic targets for cancer intervention. These findings have greatly deepened the mechanistic understandings of the regulation of alternative splicing in cancer cells, leading to rapidly growing interests in targeting cancer-related splicing defects as new therapies. Here we summarize the current research progress on splicing dysregulation in cancer and highlight the strategies available or under development for targeting RNA splicing defects in cancer.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81871878,31371299)the Shanghai Municipal Natural Science Fund(No.20ZR1406500)the Innovation Research Team of High-level Local Universities in Shanghai.
文摘RNA splicing alterations are widespread and play critical roles in cancer pathogenesis and therapy.Lung cancer is highly heterogeneous and causes the most cancer-related deaths worldwide.Large-scale multi-omics studies have not only characterized the mutational landscapes but also discovered a plethora of transcriptional and post-transcriptional changes in lung cancer.Such resources have greatly facilitated the development of new diagnostic markers and therapeutic options over the past two decades.Intriguingly,altered RNA splicing has emerged as an important molecular feature and therapeutic target of lung cancer.In this review,we provide a brief overview of splicing dysregulation in lung cancer and summarize the recent progress on key splicing events and splicing factors that contribute to lung cancer pathogenesis.Moreover,we describe the general strategies targeting splicing alterations in lung cancer and highlight the potential of combining splicing modulation with currently approved therapies to combat this deadly disease.This review provides new mechanistic and therapeutic insights into splicing dysregulation in cancer.
基金supported by the National Natural Science Foundation of China (81871878 and 31371299 to Y.B.W.31730110, 31661143031, and 31570823 to Z.F.W.)supported by the type A CAS Pioneer 100-Talent Program.
文摘RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomarkers and therapeutic targets for cancer intervention. These findings have greatly deepened the mechanistic understandings of the regulation of alternative splicing in cancer cells, leading to rapidly growing interests in targeting cancer-related splicing defects as new therapies. Here we summarize the current research progress on splicing dysregulation in cancer and highlight the strategies available or under development for targeting RNA splicing defects in cancer.